July 2011

July 25, 2011

In today's new issue of JCB, Ju et al. describe how hyperactivation of AMP-activated protein kinase (AMPK) promotes neurodegeneration in Huntington’s disease. AMPK regulates energy homeostasis and is abnormally active in the brains of both patients and mouse models of Huntington’s disease. Ju et al. show that this is probably because disrupted calcium signaling in Huntington’s neurons dysregulates AMPKs upstream activator calcium/calmodulin dependent protein kinase II. Moreover, the researchers show that hyperactivation of AMPK promotes neuronal death by reducing expression of the cell survival factor Bcl2, and that CGS26180, a drug that alleviate Huntington's disease symptoms in mice reverses this effect. You can find out more about the therapeutic implications of Ju et al.'s study in this summary.

Barnhart et al. reveal that the histone chaperone HJURP directs the formation of functional kinetochores by assembling the histone variant CENP-A into chromatin. CENP-A is a specialized version of Histone H3 that marks the position of centromeres. By targeting HJURP to ectopic chromosome regions, Barnhart et al. induced the stable incorporation of CENP-A into the underlying chromatin and the ectopic recruitment of centromere and kinetochore proteins. In addition, the researchers found that HJURP is normally correctly localized to centromeres by the Mis18 protein complex. Find out more in this short summary.

Bowen et al. report that septin GTPase filaments direct the reorganization of microtubules during epithelial polarization. Septin filaments associate with microtubules and guide the direction of microtubule growth by suppressing catastrophic depolymerization. When septins are depleted by RNAi, the microtubules in MDCK cells fail to form the polarized network characteristic of columnar epithelial cells. Our cover image shows the normal rearrangement of both septin filaments (green) and microtubules (red) as an individual MDCK cell polarizes into a columnar epithelium. You can learn why senior author Elias Spiliotis likens this process to an Amish barn raising in this week's In Focus article.

And Krzywicka-Racka and Sluder investigate why tumor cells often contain abnormally high numbers of centrosomes. One simple explanation is that cytokinesis failure causes an immediate doubling of both centrosome and chromosome number. But Krzywicka-Racka and Sluder find that repeated cleavage failure isn't sufficient to cause stable centrosome amplification within a population of untransformed cells. You can hear senior author Greenfield Sluder explain the implications of this and discuss the effects of cleavage failure on transformed cells in this weeks biobytes podcast. You can listen below, and also hear Johanna Ivaska discuss how a small GTPase and a GTPase regulatory protein compete to control integrin recycling and cell migration (Mai et al.).

Don't forget to investigate all the other great papers in today's new issue by looking at the full table of contents here.

July 11, 2011

Lander et al. demonstrate that a single E3 ubiquitin ligase regulates all four of the core transcription factors that promote epithelial to mesenchymal transitions. The F-box protein Partner of paired, or Ppa, was already known to ubiquitinate and trigger the degradation of the transcription factors Snail and Slug. Lander et al. now show that, despite their structural divergence, the transcription factors Twist and Sip1 are also targeted by Ppa, allowing EMT to be coordinately regulated by a single enzyme. You can read more in this summary.

Krumova et al. describe how the addition of the small, ubiquitin-like modifier SUMO can prevent the formation of the protein aggregates that typify Parkinson’s disease. The protein a-synuclein no longer aggregated into toxic filaments when it was sumoylated, whereas the expression of a-synuclein mutants lacking sumoylation sites increased aggregation and enhanced neurodegeneration in the substantia nigra of rats. More here.

And Gokhin and Fowler reveal that the sarcoplasmic reticulum, the membrane bound organelle that stores the calcium ions required for muscle contractions, also helps to keep the force-producing myofibrils aligned with one another. g-actin and the actin-capping protein tropomodulin3 were found to localize to the sarcoplasmic reticulum and tether it to myofibrils. In the absence of tropomodulin1, these proteins mislocalize, leading to impaired calcium release and myofibril misalignment. “We think that the sarcoplasmic reticulum itself has a role in the mechanics of the cell,” first author David Gokhin tells Mitch Leslie in this week's In Focus.

And in this month’s biosights video podcast, Richard Parton and Ilan Davis describe their research showing how a PAR-1-mediated bias in microtubule polarity directs mRNAs to the posterior of Drosophila oocytes.

Don't forget: if you'd like to discuss Parton et al.'s study in your next journal club, you can download our journal club package, containing the biosights podcast plus a pdf of the paper and all of its figures in a convenient PowerPoint file.

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